Basal Plasma Aldosterone Research Articles

PS-BPC01-2: PREDICTORS AND EFFECTS OF COMORBID ATRIAL FIBRILLATION IN HYPERTENSIVE PATIENTS DUE TO PRIMARY ALDOSTERONISM

Objective: The incidence of atrial fibrillation (AF) and risk of cardiovascular events are reportedly higher in patients with primary aldosteronism (PA) than those with essential hypertension. This study sought to determine independent predictors of comorbid AF and cardiovascular events in PA patients after PA treatment. Design and method: This nationwide registration study included PA patients more than 20 years old. Incident cardiovascular events were observed with a mean follow-up of approximately 3 years. A total of 3,654 patients with PA were included at the time of analysis. Results: Prevalence of AF was 2.4%. PA patients with AF were older, more frequently male and had longer duration of hypertension than those without AF. No significant difference in basal plasma and adrenal venous aldosterone concentration, renin activity, potassium concentration, confirmatory tests of PA, laterality or surgery rate were seen between groups. Logistic regression analysis showed age, male sex, cardiothoracic ratio, past history of coronary artery disease and heart failure were independent determinants for AF. PA patients with AF showed a higher frequency of cardiovascular events than those without AF (P < 0.001). Multivariate Cox analyses demonstrated AF in addition to duration of hypertension, older age, male sex, hypokalemia and surgery as independent prognostic factors for cardiovascular events (hazard ratio [HR] 1.866, 95% confidence interval [CI] 1.024–3.401, P < 0.05; HR 1.022, 95%CI 1.006–1.039, P < 0.01; HR 1.424, 95%CI 1.043–1.943, P < 0.05; HR 1.027, 95%CI 1.012–1.042, P = 3.2 × 10–4; HR 1.726, 95%CI 1.226–2.430, P < 0.005; HR 1.458, 95%CI 1.041–2.041, P < 0.05, respectively). After PA treatment, incidence of cardiovascular events did not differ significantly between PA patients with AF and essential hypertension patients with AF from the Fushimi registry during follow up after adjusting age, sex and prevalence of hypertension. Conclusion: Early diagnosis of PA may prevent AF and other cardiovascular events in PA patients by shortening the duration of hypertension.

PS-C31-1: SIGNIFICANCE OF SCREENING AND DIAGNOSING PRIMARY ALDOSTERONISM (PA) IN GENERAL MEDICINE

Background: Primary aldosteronism (PA) is a frequent secondary hypertension that is more frequently associated with cerebrovascular disease than essential hypertension, and thus requires appropriate diagnosis and treatment. The Japan Endocrine Society has published the new guideline for the diagnosis and treatment of primary aldosteronism, following the change of aldosterone measurement system in 2021. In this presentation, we will discuss a case of PA experienced at a dental school hospital. Case 75 years old male Current medical history: He had been diagnosed as hypertensive more than 10 years ago and had been prescribed antihypertensive medication, but he had stopped taking it. When he visited an oral surgeon for a tooth extraction, hypertension was noted and he was referred to internal medicine. <Physical findings> Blood pressure: 208/120 mmHg, Pulse: 83/min, <Biochemistry> Cre 1.09 mg/dL, Na 139mEq/L, K 3.7mEq/L. <Endocrine metabolism> fT4 0.95ng/dL, TSH 2.58micro-IU/mL, Plasma renin activity: PRA (EIA method) 0.6ng/mL/hr, Plasma aldosterone concentration: PAC (CLEIA method) 130pg/mL. <Abdominal CT> There was a nodule on the right adrenal gland. <Progress and discussion> The patient had a high aldosterone-renin ratio: ARR = PAC/PRA = 130/0.6 = 217 at the time of initial examination, and PA was suspected. CT showed a nodule in the right adrenal gland, raising suspicion of unilateral disease. Because of the high basal plasma aldosterone level and low K level, we referred the patient to a specialized facility because we thought that if PA was confirmed by functional confirmation testing, the case could be aggressively localized and typed by adrenal vein sampling (AVS). In this presentation, we would like to discuss the significance of screening and diagnosis of PA in primary care and general practice settings such as dental school hospitals, based on the results of functional confirmation testing at specialized facilities, and in light of current guidelines.

Biochemical Evaluation by Confirmatory Tests after Unilateral Adrenalectomy for Primary Aldosteronism.

Primary aldosteronism (PA) is the most common cause of endocrine hypertension. Unilateral PA can be cured using unilateral adrenalectomy (Adx). PA surgery outcome (PASO) criteria, which include clinical and biochemical outcomes, have been proposed to evaluate PA cure after Adx. However, clinical outcomes are often inconsistent with biochemical outcomes. In addition, although confirmatory tests are included as endpoints of biochemical outcomes in the PASO criteria, their clinical usefulness has not yet been established. We evaluated clinical parameters and confirmatory test results before and after Adx in 16 patients with PA and assessed the usefulness of the confirmatory tests. The following were the clinical outcomes after Adx: 37.5% complete success, 62.5% partial success, and 0% absent success. The ratio of biochemical complete success was as follows: 69% aldosterone/renin ratio and basal plasma aldosterone concentration, 19% as assessed by the captopril challenge test, 47% as assessed by the saline infusion test, 30% as assessed by the furosemide upright test, and 100% urine aldosterone. Of these, biochemical complete success was judged in four cases by aldosterone/renin ratio and basal plasma aldosterone concentration, one case by captopril challenge test, five cases by saline infusion test, and one case by furosemide upright test. Although clinical outcomes and urine aldosterone levels improved after Adx, confirmatory tests failed to improve in some cases. The current criteria are not considered useful for biochemical evaluation after Adx. To determine whether additional treatment with mineralocorticoid receptor antagonists is required, more accurate biochemical criteria should be established after Adx.

LBODP024 Successful Adrenal Vein Sampling Using Dexamethasone Premedication In Patients With Iodine Contrast Media Allergy

Abstract Background Preparation of patients with iodine contrast media (ICM) allergy who require adrenal vein sampling (AVS) to establish source of aldosterone excess in confirmed primary aldosteronism (PA) is controversial. Usual premedication with high dose prednisone can interfere with cortisol determinations, possibly altering the aldosterone-to-cortisol ratios for the identification of lateralized aldosterone excess. Objective Evaluate the efficacy and safety of premedication with high dose dexamethasone to perform AVS in patients with ICM. Methods 177 consecutive patients with confirmed PA who underwent bilateral simultaneous basal and post ACTH bolus AVS at our center between January 2010 and December 2020 were retrospectively analyzed for reported ICM allergy. A total of 7 patients (4%) with history of allergic reactions to ICM were premedicated with three doses of 7.5 mg dexamethasone rather than the usual 50 mg of prednisone. Results No breakthrough allergic reactions were reported in the 7 patients. The mean age at the time of AVS procedure was 55.1 ± 16.8 years. Patients had been hypertensive for a mean of 6.7 ± 5.9 years. The mean systolic blood pressure on the day of the procedure was 137.4 ± 4.2 mmHg and the mean diastolic blood pressure 77.1 ± 12.9 mmHg. Most patients had at least 2 anti-hypertensive medications in their drug regimen prior to AVS procedure, none being mineralocorticoid receptor antagonists. Dexamethasone suppression effect on AVS: All basal peripheral cortisol levels were suppressed, < 50 nmol/L, confirming lack of meaningful cortisol co-secretion. The basal and post-ACTH selectivity index were respectively >2 and > 5 bilaterally in all patients, confirming adequate cannulation of both adrenal veins. Basal peripheral plasma aldosterone concentration (PAC) was also reduced by dexamethasone administration by an average of 66 ± 30% in comparison with PAC measured before AVS. Despite basal suppression, PAC increased following ACTH bolus injection with an average rise of 698.8 ± 644.5% from baseline. AVS results: Four patients had lateralized (A/C ratio > 2 basally and >4 post ACTH), while three had bilateral source according to AVS results. Follow up data for a mean of 58 ± 41.4 months was available for 6 patients. In the three patients who underwent unilateraladrenalectomy for lateralized source, basal and post-ACTH lateralization ratios were concordant. All 3 patients had contralateral suppression, confirmed adrenocortical adenoma at histopathology and clinical (n=3) (normal blood pressure without medication) and/or biochemical cure (n=2) (direct renin concentration > 10 ng/dL) at follow up. Conclusion AVS using dexamethasone premedication is safe and accurate for diagnosing source of aldosterone excess in patients with PA and ICM allergy. Presentation: No date and time listed

Associated factors and effects of comorbid atrial fibrillation in hypertensive patients due to primary aldosteronism.

The incidence of atrial fibrillation (AF) and risk of cardiovascular events are reportedly higher in patients with primary aldosteronism (PA) than essential hypertension. However, associated factors of comorbid AF and cardiovascular events in PA patients after PA treatment remain unclear. This nationwide registration study included PA patients ≥20 years old. Incident cardiovascular events were observed with a mean follow-up of approximately 3 years. A total of 3654 patients with PA were included at the time of analysis. Prevalence of AF was 2.4%. PA patients with AF were older, more frequently male and had longer duration of hypertension than those without AF. No significant difference in basal plasma and adrenal venous aldosterone concentration, renin activity, potassium concentration, confirmatory tests of PA, laterality or surgery rate were seen between groups. Logistic regression analysis showed age, male sex, cardiothoracic ratio, past history of coronary artery disease and heart failure were independent factors associated with AF. PA patients with AF showed a higher frequency of cardiovascular events than those without AF (P < 0.001). Multivariate Cox analyses demonstrated AF in addition to older age, duration of hypertension, body mass index and chronic kidney disease as independent prognostic factors for cardiovascular events after PA treatment. Incidence of cardiovascular events were significantly lower in PA patients with AF than AF patients from the Fushimi registry during follow-up after adjusting age, sex and systolic blood pressure. Early diagnosis of PA may prevent AF and other cardiovascular events in PA patients by shortening the duration of hypertension and appropriate PA treatment.

Evaluation of Patients Performed with Saline Infusion Test with a Pre-Diagnosis of Primary Hyperaldosteronism

Background: Primary hyperaldosteronism (PHA) is a primarily treatable cause of arterial hypertension characterized by low plasma renin and high aldosterone levels. The prevalence of secondary hypertension as a common endocrine cause is 5-13%. The plasma aldosterone/renin ratio (ARR) is the best available method for PHA screening. One or more confirmatory tests may be required to confirm or exclude patients' diagnoses. One frequently used confirmatory test is the saline infusion test (SİT). We aimed to screen the patients who underwent SİT with the preliminary diagnosis of PHA and to compare the results of the patients diagnosed with essential hypertension (EH) and PHA.&#x0D; Material and Methods: Seventy-seven patients with a history of drug-resistant hypertension or unexplained spontaneous or diuretic-induced hypokalemia or adrenal incidentaloma, or a family history of early-onset hypertension or cerebrovascular accident at a young age (0.05). Basal plasma aldosterone (p

Atrial fibrillation is an independent predictor of cardiovascular events in patients with primary aldosteronism

Abstract Background A higher risk of cardiovascular events has been reported in patients with hypertension due to primary aldosteronism (PA) than essential hypertension. This study sought to determine the independent predictors for the risk of cardiovascular events in hypertensive patients with PA. Methods The Japan Primary Aldosteronism Study (JPAS) has retrospectively recruited 3,654 patients with PA between January 2006 and January 2019 as a nationwide registry and we evaluated the differences between patients with and without AF from these data. The patients underwent general laboratory test, electrocardiography, echocardiography, diagnostic confirmatory tests including saline-loading, captopril-challenge, and upright furosemide-loading tests and adrenal venous sampling (AVS). We evaluated the cardiovascular events including myocardial infarction, stroke, heart failure and renal failure, with a mean follow-up duration of approximately 4 years. Results The prevalence of AF was 2.4% (88/ 3,654). PA patients with AF were older (60.3 vs 52.8 years old), more male (77.3% vs 46.6%) and had longer duration of hypertension (14.3 vs 8.3 years) than those without AF. Each prevalence of cerebral infarction (12.5% vs 3.5%), chronic kidney disease (12.5% vs 4.8%), coronary artery disease (CAD) (10.2% vs 1.7%), heart failure (5.7% vs 0.7%) and left ventricular hypertrophy evaluated by echocardiography (46.4% vs 31.9%) was higher in PA patients with AF. Patients with AF had more kinds of antihypertensive drugs (1.3 vs 1.1). There was no significant difference of basal plasma aldosterone concentration (PAC), plasma renin activity, each confirmatory tests, lateralized ratio in AVS after stimulation with adrenocorticotropic hormone (ACTH) and laterality between the 2 groups. Logistic regression analysis showed that age, cardiothoracic ratio (CTR), past history of CAD and heart failure were independent determinants for AF. PA patients with AF had higher rates of cardiovascular events compared to those without AF (Figure, P&amp;lt;0.005). Multivariate Cox regression analyses demonstrated AF in addition to adrenal PAC before ACTH stimulation, age, hypokalemia and duration of hypertension as independent prognostic factors for cardiovascular events (hazard ratio [HR] 1.993, 95% confidence interval [CI] 1.042–3.815, P&amp;lt;0.05; HR 1.ehab724.231608, 95% CI 1.ehab724.231604–1.ehab724.231612, P&amp;lt;0.0005; HR 1.03, 95% CI 1.012–1.048, P&amp;lt;0.005; HR 1.748, 95% CI 1.242–2.461, P&amp;lt;0.005; HR 1.029, 95% CI 1.013–1.044, P&amp;lt;0.0005, respectively). Conclusions This study provides evidence that comorbid AF is associated with older age, male sex, X-ray CTR and prevalence of CAD and heart failure. Furthermore, AF is an independent predictor of cardiovascular events in patients with PA, in addition to the adrenal venous concentration of aldosterone, hypokalemia, older age and duration of hypertension. Earlier recognition and intervention of AF can prevent cardiovascular events in PA. Funding Acknowledgement Type of funding sources: None. Figure 1

Mild Autonomous Cortisol Secretion in Primary Aldosteronism Enhances Renal and Hemorrhagic Cerebrovascular Complications

Background: It is well known that primary aldosteronism (PA) is often associated with renal dysfunction and cardiovascular events (CVEs). However, the synergic effect of mild autonomous cortisol secretion (MACS) on the co-morbidities among PA has not been clarified yet. Thus, we retrospectively assessed whether the presence of MACS in PA patients with adrenal tumor, which may have MACS, to enhance the risk of the complications using a large Japanese multicenter database. Methods: We enrolled patients with both confirmed PA and obvious adrenal tumor (diameter > 1 cm) on computed tomography. The subtype of PA was diagnosed based on the results of adrenal venous sampling with ACTH stimulation. A total of 575 study subjects were stratified into two groups according to 1-mg dexamethasone suppression test (DST) results (cut-off post-DST serum cortisol 1.8 µg/dL): MACS group (N=174, 30.2%) and non-MACS group (N=401, 69.8%). Decreased estimated glomerular filtration rate (eGFR) was defined as <60 ml/min per 1.73m2. Results: The percentage of unilateral PA between the MACS and non-MACS group was equivalent (50.0% vs. 48.1%). Prevalence of decreased eGFR in the MACS group was higher than in the non-MACS group [odds ratio (OR) 1.91, 95% confidence interval (95% CI) 1.20–3.04, P=0.006]. Conversely, prevalence of MACS was higher in patients with decreased eGFR than those without decreased eGFR (42.7% vs 28.0%, P=0.008). Proteinuria was deteriorated with the increase in post-DST serum cortisol concentration as well as the basal plasma aldosterone concentration (PAC) (P=0.028 and P<0.001, respectively), although PAC but not the presence of MACS was selected as an independent factor related with decreased eGFR. Prevalence of cerebral hemorrhage in the MACS group was higher than the non-MACS group. (OR 5.35, 95%CI 1.83–15.6, P=0.002). We found that MACS was the only significant factor which increased the odds of developing cerebral hemorrhage (OR 9.13, 95%CI 2.15–38.90, P=0.003). Prevalence of other CVEs between the two groups was similar. Regardless of the PA subtype, complication rate of decreased eGFR and cerebral bleeding in the MACS group were significantly or tend to be higher than non-MACS group. Conclusion: Our date strongly suggested that co-secretion of cortisol in PA directly and/or indirectly increase renal and cerebrovascular comorbidities. Given that MACS is common in PA, endocrinological testing with DST is recommended in PA patients, especially those with adrenal tumor on imaging. (Supported by Research Grants of AMED:JP17ek0109122, JP20ek0109352; National Center for Global Health and Medicine:27–1402, 30–1008), and Ministry of Health, Labour, and Welfare, Japan (046).

Primary Aldosteronism with Parathyroid Hormone Elevation: A Single-center Retrospective Study.

Objective Primary aldosteronism (PA) is a major cause of secondary hypertension. The association between PA and other hormone disorders is unclear. The present study aimed to evaluate whether the parathyroid hormone (PTH) value is associated with PA subtypes or specific treatments. Methods We enrolled 135 patients with PA who had their PTH value measured before undergoing a specific treatment. We evaluated whether PTH value is associated with PA subtypes or with specific treatments. The present study is a single-center retrospective study (2011-2018). Results Our study showed that, among the patients with PA, the proportion of those with PTH elevation was >30%. The PTH value was significantly correlated with both the basal plasma aldosterone concentration (PAC) and PAC after a captopril challenge test. However, the PTH value was not significantly different between the patients with unilateral and bilateral PA. We observed that the serum PTH value decreased after treatment of PA with unilateral adrenalectomy or mineralocorticoid receptor antagonists. Conclusion Our findings suggest that the PTH value in PA patients might be associated with the autonomous production of aldosterone. However, there was no correlation between the PTH value and PA subtypes in our study. Additionally, our study showed that targeted treatment for PA may lead to a decrease in the serum PTH levels. Hence, the PTH value could potentially be used as an index for measuring the suitability for PA treatment.

Hypertension Editors' Picks: Hyperaldosteronism.

Hypertension Editors' Picks: Hyperaldosteronism.

Abstract 13211: Atrial Fibrillation is an Independent Predictor for Cardiovascular Events in Hypertensive Patients Due to Primary Aldosteronism

Introduction: A higher risk of cardiovascular events has been reported in patients with hypertension due to primary aldosteronism (PA) than essential hypertension. Hypothesis: This study sought to determine the independent predictors for the risk of cardiovascular events in hypertensive patients with PA. Methods: The nation-wide PA registration study (JPAS/JRAS) included patients aged 20 years and older. Data were collected between January 2006 and January 2019, with a mean follow-up duration of approximately 4 years. Characteristics of patients with or without atrial fibrillation (AF) on the diagnosis of PA were compared. Patients were treated by surgery or MR antagonists and incident cardiovascular events were followed up. Results: A total of 3,647 patients with PA were included at the time of analysis. Prevalence of AF was 2.4% (87/ 3,647). PA patients with AF were older, more male and had longer duration of hypertension than those without AF. Each prevalence of cerebral infarction, chronic kidney disease, coronary artery disease, heart failure and left ventricular hypertrophy evaluated by echocardiography was higher in PA patients with AF than those without AF. Patients with AF had more kinds of antihypertensive drugs. There was no significant difference of basal plasma aldosterone concentration, plasma renin activity, unilateral subtype and rate of surgery between the 2 groups. PA patients with AF had higher rates of cardiovascular events compared to those without AF (14.9% vs 6.7%, P=0.002). Multivariate cox regression analyses demonstrated AF in addition to older age, male gender, duration of hypertension and surgery performance as an independent prognostic factor for cardiovascular events (HR, 1.950 [95%CI, 1.021-3.726], P&lt;0.05; HR, 1.023 [95%CI, 1.008-1.039], P=0.003; HR, 1.385 [95%CI 1.025-1.870], P&lt;0.05; HR, 1.023 [95%CI, 1.008-1.038], P=0.002; HR, 1.580 [95%CI, 1.168-2.138], P=0.003;respectively). Conclusions: Among patients with PA, male gender, older age, and longer duration of hypertension are the predisposing factors of AF in PA patients. In addition, AF was an independent risk factor for cardiovascular events in PA patients. It is warranted to prevent and to treat appropriately AF in patients with PA.

MON-198 Cosyntropin Stimulation on Adrenal Venous Sampling Obscure Surgically Curable Primary Aldosteronism

Context: While it has been shown that ACTH stimulation during adrenal venous sampling (AVS) for primary aldosteronism (PA) leads to correct lateralization, others showed opposite results. Whether to use ACTH stimulation during AVS for the subtype diagnosis of PA remains unsolved. Objectives: Our purpose of this study is to evaluate the clinical implications of ACTH stimulation during AVS in terms of surgical outcomes. Design and settings: Among JRAS cohort, we allocated 314 patients with both basal and ACTH-stimulated AVS data who underwent adrenalectomy to 3 groups: basal lateralization index (LI)≥2 with ACTH-stimulated LI ≥4 on the ipsilateral side (Unilateral (U) to U group, n=245); basal LI <2 with ACTH-stimulated LI ≥4 (n=15); basal LI≥2 with ACTH-stimulated LI <4 (U to Bilateral (B) group, n=54). We compared surgical outcomes among the groups. Results: Compared with the U to U group, the U to B group had poor clinical and biochemical outcomes and low rates of adrenal adenoma as a pathological finding. All patients in the U to Bgroup with clinical and biochemical benefits however had adrenal adenoma as a pathological finding and could be well differentiated from those with poor surgical outcome via basal LI, but not ACTH-stimulated LI. A receiver operating characteristic curve analysis demonstrated that the cut-off value of 8.3 showed the specificity of 84% for the prediction of good surgical outcome in U to B group.These results were similar even when we defined each group based on a cut-off value of 4 for basal LI. Although, the basal plasma aldosterone concentration (PAC) in the adrenal veins on both dominant and non-dominant sides among patients with better surgical outcome in the U to B group were not significantly different from those in the U to U group, there was a significant difference in the ACTH-stimulated PAC on the dominant side. Conclusions: We demonstrated novel findings showing that patients in the U to B group were shown to be comprised of 2 groups with good and poor surgical outcomes, and basal LI was useful in identifying PA patients with good surgical outcome in U to B group. The low expression level of MC2R receptor on aldosterone-producing adenoma (APA) might be the explanation of the weak response in aldosterone level in a proportion of surgically curable APA cases. These findings point to the important fact that ACTH stimulation on AVS obscure surgically curable cases of PA.

Nadir Aldosterone Levels After Confirmatory Tests Are Correlated With Left Ventricular Hypertrophy in Primary Aldosteronism.

Left ventricular hypertrophy (LVH) is often seen in patients with primary aldosteronism (PA), and the prevalence of LVH is reportedly higher among patients with PA than patients with essential hypertension. However, the correlation between aldosterone levels and LVH is undefined, and how aldosterone affects LVH in patients with PA remains unclear. We, therefore, retrospectively assessed a large PA database established by the multicenter JPAS (Japan Primary Aldosteronism Study) to reveal the factors associated with LVH in patients with PA without suspected autonomous cortisol secretion. In the 1186 patients with PA studied, the basal plasma aldosterone concentration, plasma renin activity, and the aldosterone-to-renin ratio did not significantly correlate with left ventricular LV mass index (LVMI) in single or multiple regression analyses. However, the plasma aldosterone concentration after the captopril challenge test or saline-infusion test, which are associated with autonomous aldosterone secretion, correlated significantly with LVMI, even after adjusting for patients' backgrounds, including age and blood pressure. In addition, hypokalemia and the unilateral subtype also correlated with LVMI. Longitudinal subanalysis of medically or surgically treated patients with PA showed significant reductions in LVMI in both the surgery (63.0±18.1 to 55.3±19.5 g/m2.7, P<0.001) and drug treatment (56.8±14.1 to 52.1±13.5 g/m2.7, P<0.001) groups. Our results suggest the autonomous aldosterone secretion level, not the basal aldosterone level itself, is relevant to LVH in patients with PA. In addition, the elevated LVMI seen in patients with PA is at least partially reversible with surgical or medical treatment.

Basal Plasma Aldosterone Concentration Predicts Therapeutic Outcomes in Primary Aldosteronism.

PurposeNormal basal plasma aldosterone concentration (PAC) reflects mild aldosterone excess compared to high basal PAC. We previously reported lower risk for cardiovascular and cerebrovascular events in patients with primary aldosteronism (PA) and normal basal PAC (nPA) than in those with high basal PAC (hPA). However, the differences in therapeutic outcomes between nPA and hPA are unclear. The aim of this multi-institutional, retrospective cohort study was to determine the clinical significance of nPA to therapeutic outcomes, including adrenalectomy (ADX) and treatment with mineralocorticoid receptor antagonists (MRAs).MethodsA total of 1146 patients with PA who were diagnosed and underwent adrenal venous sampling (AVS) between January 2006 and October 2016 were enrolled. The clinical parameters at baseline and after ADX or treatment with MRA were compared between the nPA and hPA groups.ResultsSignificantly higher rates of absent clinical success (36.6 vs. 21.9%, P = 0.01) and absent biochemical success (26.4 vs. 5.2%, P < 0.01) were found for the nPA group than for the hPA group, respectively. Logistic regression analysis identified baseline PAC as a significant independent predictor of absent clinical success of ADX and MRAs.ConclusionsPlasma aldosterone concentration at baseline was a significant and independent predictor of absent clinical success of ADX and MRA. Mineralocorticoid receptor antagonist treatment appeared to be a better therapeutic choice than ADX in the nPA group.

P3562Efficient selection of patients with aldosterone-producing adenoma using the ACTH stimulation test

Abstract Adrenal venous sampling (AVS) is the gold standard test for distinguishing between unilateral and bilateral primary aldosteronism (PA), however, AVS requires advanced and time consuming technique. The needs for AVS has been increasing due to increased utilization of screening for PA. Efficient selection of unilateral PA, such as aldosterone-producing adenoma (APA), before AVS is useful to avoid undesirable AVS in bilateral PA, such as idiopathic hyperaldosteronism. In this study, 40 patients who underwent all three confirmatory tests including the captopril-challenge test, furosemide upright test and adrenocorticotropin (ACTH) stimulation test (AST), and who were diagnosed as having PA by AVS were recruited. Subjects were diagnosed as having unilateral aldosterone excess (n=22) or bilateral aldosterone excess (n=18) by AVS. All patients with unilateral PA underwent operation and were finally diagnosed with APA. Major differences were detected in serum potassium level, basal plasma aldosterone concentration (PAC), presence of adrenal tumor, and AST results between the two groups. The PAC/cortisol ratio at 120 min in the AST showed the highest diagnostic capability for distinguishing the subtype of PA according to a receiver operating characteristic (ROC) curve analysis (area under the ROC curve was 0.956). At a cut-off value of 1.20 for the PAC/cortisol ratio at 120 min on AST, the sensitivity was 95.5% and the specificity was 88.9%. Sufficiently high sensitivity demonstrated indicates that the PAC/cortisol ratio at 120 min in the AST is useful for selecting patients with PA who are suitable for AVS.

SUN-366 The Optimal Cutoff Value for Basal Plasma Aldosterone Concentration Suspected as Primary Aldosteronism Distributed According to Aldosterone-Renin Ratio and Confirmatory Tests Response

Aldosterone/renin ratio (ARR) >200 [(pg/mL)/(ng/mL/hr)] is a widely accepted threshold to screen for primary aldosteronism (PA) (1). Because using ARR as a sole index leads to excessive inclusion of cases with low renin essential hypertension, it may be desirable to combine ARR with a minimum plasma aldosterone concentration (PAC) value to increase diagnostic accuracy, but currently there is no consensus on the minimum PAC value. Therefore, we carried out a single-center, retrospective study to investigate optimal PAC cutoff to be used with ARR >200. The subjects were 385 individuals (240 female and 145 male) with ARR >200 who underwent PA screening tests between 2010 and 2015. They were diagnosed according to the Japan Endocrine Society guideline (2) with either PA or essential hypertension (EH). The optimal cutoff value for baseline PAC that best distinguished between PA and EH was calculated. Of the 385 subjects, 297 were diagnosed with PA and 88 with EH. Of 194 PA patients who underwent adrenal venous sampling, 141 exhibited aldosterone hypersecretion from both adrenal glands, and 53 were diagnosed with aldosterone-producing adenoma (APA) on the basis of adrenalectomy. There was no difference between the PA (n = 194) and EH (n = 88) groups in terms of age, body mass index, or glucose and lipid profiles. Receiver operating characteristic curve analysis found that the optimal baseline PAC for distinguishing between PA and EH was 171 pg/mL, which provided a sensitivity of 0.75 and a specificity of 0.65 (area under the curve 0.718 and 95% confidence interval 0.656-0.780). Baseline PAC was ≥171 pg/mL for all 53 subjects with APA (minimum 171 pg/mL, maximum 943 pg/mL, and median 341 pg/mL), and if the cutoff value for baseline PAC is set at 171 pg/mL, it is unlikely that significant cases of APA will be overlooked in PA screening using ARR >200. Combining PAC ≥171 pg/mL with ARR >200 increases diagnostic accuracy for PA without compromising APA detection. Reference: (1)Hiramatsu et al., Arch Intern Med. 1981 Nov;141(12):1589-93. (2) Nishikawa et al., Endocr J. 2011;58(9):711-21.

Efficient screening of patients with aldosterone-producing adenoma using the ACTH stimulation test.

Adrenal venous sampling (AVS) is the gold standard test for distinguishing between unilateral and bilateral primary aldosteronism (PA); however, AVS requires advanced and time consuming technique. The needs for AVS have been increasing due to the increased utilization of screening for PA. An efficient selection of unilateral PA, such as aldosterone-producing adenoma (APA), before AVS is useful to avoid undesirable AVS in bilateral PA, such as idiopathic hyperaldosteronism. In this study, 40 patients who received all three confirmatory tests, including the captopril challenge test, furosemide upright test and adrenocorticotropin (ACTH) stimulation test (AST), and who were diagnosed as having PA by AVS were recruited. Subjects were diagnosed as having unilateral aldosterone excess (n = 22) or bilateral aldosterone excess (n = 18) by AVS. All patients with unilateral PA underwent an operation and were finally diagnosed with APA. Major differences were detected in serum potassium level, basal plasma aldosterone concentration (PAC), presence of adrenal tumor, and AST results between the two groups. The PAC/cortisol ratio at 120 min in the AST showed the highest diagnostic capability for distinguishing the subtypes of PA according to a receiver operating characteristic (ROC) curve analysis (area under the ROC curve was 0.956). At a cutoff value of 1.20 for the PAC/cortisol ratio at 120 min on the AST, the sensitivity was 95.5%, and the specificity was 88.9%. This sufficiently high sensitivity suggests that the PAC/cortisol ratio at 120 min in the AST could be useful for the screening of patients with PA who are suitable for AVS.

Dysregulation of Aldosterone Secretion in Mast Cell-Deficient Mice.

Resident adrenal mast cells have been shown to activate aldosterone secretion in rat and man. Especially, mast cell proliferation has been observed in adrenal tissues from patients with aldosterone-producing adrenocortical adenoma. In the present study, we show that the activity of adrenal mast cells is stimulated by low-sodium diet and correlates with aldosterone synthesis in C57BL/6 and BALB/c mice. We have also investigated the regulation of aldosterone secretion in mast cell-deficient C57BL/6 KitW-sh/W-sh mice in comparison with wild-type C57BL/6 mice. KitW-sh/W-sh mice submitted to normal sodium diet had basal plasma aldosterone levels similar to those observed in wild-type animals. Conversely, low-sodium diet unexpectedly induced an exaggerated aldosterone response, which seemed to result from an increase in adrenal renin and angiotensin type 1 receptor expression. Severe hyperaldosteronism was associated with an increase in systolic blood pressure and marked hypokalemia, which favored polyuria. Adrenal renin and angiotensin type 1 receptor overexpression may represent a compensatory mechanism aimed at activating aldosterone production in the absence of mast cells. Finally, C57BL/6 KitW-sh/W-sh mice represent an unexpected animal model of primary aldosteronism, which has the particularity to be triggered by sodium restriction.

Favorable surgical outcomes of aldosterone-producing adenoma based on lateralization by CT imaging and hypokalemia: a non-AVS-based strategy

To test the efficacy of a strategy based on CT imaging and clinical characteristics on lateralizing origin of excess aldosterone secretion in primary aldosteronism. Consecutive patients with diagnosed primary hyperaldosteronism from June 2006 to July 2012 in our center underwent adrenal surgeries without pre-operational adrenal venous sampling (AVS) if all the three criteria were met: (1) round- or oval-shaped occupational lesion of low density after contrast enhancement with diameter >1cm on CT scan was located in one adrenal gland; (2) unequivocally normal contralateral adrenal gland; (3) serum potassium level lower than 3.5mmol/L. Subjects who had received operation were taken into analysis and follow-ups. One hundred and twenty-five patients fulfilled the criteria and were recruited into our research. One hundred and twenty-two operated patients (97.6%) experienced complete resolution of hypokalemia as well as resolution or improvement in hypertension with reduction in antihypertensive medication, while 3 patients (2.4%) failed to obtain normal kalemia and continued on spironolactone therapy. At a median of 65-month (range 21-93) follow-up of these 122 subjects, 27 patients dropped out (22.1%). The 95 responding patients reported no episodes of paralysis or confirmed hypokalemia or any supplementation of potassium. Multivariate linear correlation analysis showed that plasma potassium level was correlated inversely with tumor diameter (r=-0.258, 95% CI -0.076, -0.514, p=0.037) and basal plasma aldosterone level (r=-0.251, 95% CI -0.040, -0.464, p=0.042). Most patients with typical unilateral adrenal macroadenomas, normal contralateral glands and hypokalemia could attain favorable surgical therapeutic outcomes without pre-operational AVS lateralization.

L-Lysine Acts as a Serotonin Type 4 Receptor Antagonist to Counteract In Vitro and In Vivo the Stimulatory Effect of Serotonergic Agents on Aldosterone Secretion in Man.

In the normal human adrenal gland, serotonin (5-HT) stimulates aldosterone secretion through the 5-HT4 receptor (5-HT4R). However, the physiological role of the serotonergic control of adrenocortical function is not known. In the present study, we have investigated the ability of l-Lysine, which has been shown to act as a 5-HT4 receptor antagonist, to counteract in vitro and in vivo the stimulatory effect of 5-HT4R agonists on aldosterone production. l-Lysine was found to inhibit aldosterone production induced by 5-HT and the 5-HT4R agonists BIMU8 from cultured human adrenocortical cells. The action of l-Lysine (4.95 g/day orally) on the adrenal cortex was also evaluated in 20 healthy volunteers in a double blind, cross-over, placebo controlled study. l-Lysine had no significant influence on basal plasma aldosterone levels and the aldosterone responses to upright posture, tetracosactide, and low sodium diet (10 mmol/day for 3 days). Conversely, l-Lysine significantly reduced the surge of plasma aldosterone induced by metoclopramide indicating that l-Lysine is able to efficiently antagonize the adrenal 5-HT4 receptors in vivo. These results suggest that l-Lysine supplementation may represent a new treatment of primary adrenal diseases in which corticosteroid hypersecretion is driven by overexpressed 5-HT4 receptors.